Toxicology

Hepatotoxicity

TRHepatotoksisite
Also known as:Drug-induced liver injury · DILI · Liver toxicity

Liver injury caused by a drug, herbal or dietary supplement or other chemical, ranging from asymptomatic aminotransferase elevation to cholestasis, hepatitis and acute liver failure.

Formula

R = (ALT / ULN) / (ALP / ULN)

In depth

Intrinsic injury is predictable and dose-related, as when the reactive paracetamol metabolite NAPQI overwhelms glutathione; idiosyncratic injury is rare, not clearly dose-related and often immune-mediated or HLA-linked (e.g. flucloxacillin and HLA-B*57:01). Mechanisms include reactive metabolites, mitochondrial toxicity, bile salt export pump inhibition and immune activation; alcohol, pre-existing liver disease, enzyme induction and slow acetylation (isoniazid) add risk.

The injury pattern is classified by the R ratio (ULN, upper limit of normal): hepatocellular R ≥ 5, cholestatic R ≤ 2, mixed in between. Hy’s law (ALT > 3 × ULN plus total bilirubin > 2 × ULN, without cholestasis or another cause) flags a high risk of severe injury. Causality is assessed with RUCAM.

Clinical pearl

Withdraw the suspected drug promptly when liver injury is accompanied by jaundice or symptoms, and avoid rechallenge; for higher-risk drugs (e.g. isoniazid, methotrexate, valproate) check baseline liver tests and warn patients about anorexia, nausea, dark urine and jaundice.

Example drugs

paracetamol Isoniazid amoxicillin/clavulanic acid Flucloxacillin Valproic acid Methotrexate
TRIn Turkish

Hepatotoksisite

İlaçların, bitkisel ürünlerin, diyet takviyelerinin ya da diğer kimyasal maddelerin neden olduğu karaciğer hasarıdır; asemptomatik aminotransferaz yüksekliğinden kolestaz, hepatit ve akut karaciğer yetmezliğine kadar geniş bir yelpazede görülür.

İntrinsik hasar öngörülebilir ve doza bağımlıdır; parasetamolün reaktif metaboliti NAPQI’nin glutatyon kapasitesini aşması buna örnektir. İdiyosenkratik hasar ise nadirdir, dozla belirgin ilişki göstermez ve sıklıkla immün aracılı ya da HLA ilişkilidir (ör. flukloksasilin ve HLA-B*57:01). Mekanizmalar arasında reaktif metabolitler, mitokondriyal toksisite, safra tuzu dışa atım pompasının inhibisyonu ve immün aktivasyon yer alır; alkol, önceden var olan karaciğer hastalığı, enzim indüksiyonu ve yavaş asetilasyon (izoniazid) riski artırır.

Hasar paterni R oranıyla sınıflandırılır (ULN: normalin üst sınırı): R ≥ 5 hepatoselüler, R ≤ 2 kolestatik, arada kalan değerler mikst hasardır. Hy yasası (ALT > 3 × ULN ile birlikte total bilirubin > 2 × ULN; kolestaz veya başka neden yok) ağır hasar riskinin yüksek olduğunu gösterir. Nedensellik RUCAM ile değerlendirilir.

Sarılık ya da semptomlarla seyreden karaciğer hasarında şüpheli ilaç derhal kesilmeli ve yeniden denenmemelidir; riskli ilaçlarda (ör. izoniazid, metotreksat, valproat) başlangıç karaciğer testleri yapılmalı, hasta iştahsızlık, bulantı, koyu idrar ve sarılık için uyarılmalıdır.

Diğer adları:İlaca bağlı karaciğer hasarı · Karaciğer toksisitesi · Hepatotoksik etki
Updated 24.09.2026 0 views Educational reference — verify against current sources before clinical use.

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